Metabolic disorders are a collection of health disorders that increase the risk of morbidity and loss of qualify of life. Examples of metabolic disorders include diabetes, obesity, including central obesity (disproportionate fat tissue in and around the abdomen), atherogenic dyslipidemia (these include a family of blood fat disorders, e.g., high triglycerides, low HDL cholesterol, and high LDL cholesterol that can foster plaque buildups in the vascular system, including artery walls), high blood pressure (130/85 mmHg or higher), insulin resistance or glucose intolerance (the inability to properly use insulin or blood sugar), a chronic prothrombotic state (e.g., characterized by high fibrinogen or plasminogen activator inhibitor-1 levels in the blood), and a chronic proinflammatory state (e.g., characterized by higher than normal levels of high-sensitivity C-reactive protein in the blood). Metabolic disorders afflict more than 50 million people in the United States.
Obesity represents the most prevalent of metabolic disorders, afflicting more than 26 percent of U.S. adults. Obesity increases the risk of a wide range of obesity-associated disorders, including high blood pressure, arthritis, elevated cholesterol, coronary artery disease, hypertension, stroke, diabetes, hyperlipidemia and some cancers. (See, e.g., Nishina, P. M. et al. (1994), Metab. 43:554-558; Grundy, S. M. & Barnett, J. P. (1990), Dis. Mon. 36:641-731, each of which is expressly incorporated by reference). Obesity is the second leading cause of premature death in the U.S.
There is therefore a great need for new methods for the treatment of metabolic disorders such as obesity and for the identification of novel agents useful in the prevention and treatment of such disorders.